PURPOSE OF REVIEW Recent discoveries relay commensal gut microbiota as a relevant factor in the maintenance of intestinal homeostasis. RECENT FINDINGS Alterations in the composition of the intestinal microbiota have been reported in patients with systemic lupus erythematosus and many other inflammatory and autoimmune conditions. However, the mechanisms by which the intestinal microbiota can influence systemic immunity in these situations remain to be elucidated. The inappropriate immune responses of patients with systemic lupus erythematosus could originate a breakdown of tolerance towards the microbiota, leading to the expansion and/or contraction of specific bacterial groups that may culminate in a dysbiotic state. Conversely, an altered composition of the intestinal microbiome in genetically predisposed individuals could influence systemic immunity by several mechanisms, leading to a breakdown of tolerance to self-antigens. Moreover, humoral immune responses can be affected by specific bacterial groups in these individuals. SUMMARY Recent findings support an important role for the crosstalk between bacteria and immune cells to maintain an intestinal homeostasis crucial to sustain tolerance toward self-antigens and intestinal microbiota.